, Volume 40, Issue 3, pp 884–893 | Cite as

Effects of Ergosterol on COPD in Mice via JAK3/STAT3/NF-κB Pathway

  • Wang Huan
  • Zhang Tianzhu
  • Li YuEmail author
  • Wang ShuminEmail author


The present study was to evaluate the effect of ergosterol (ER) on CS (cigarette smoke)-induced chronic obstructive pulmonary disease (COPD) in mice. Fifty male ICR mice were randomly assigned to five groups: control group, CS group, CS + dexamethasone (Dex, 2 mg/kg) group, CS + ER (ER, 25 mg/kg) group, CS + ER (ER, 50 mg/kg). H&E staining demonstrated that ER inhibited CS-induced pathological injury in lung tissue. Besides, ER could restore the activities of superoxide dismutase (SOD) in serum and in the lung, catalase (CAT) in serum and reduce the content of malondialdehyde (MDA) in serum and in the lung. ER also inhibited pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in serum and the lung. Furthermore, ER significantly inhibited the protein expression of JAK3/STAT3/NF-κB pathway in CS-induced mice. Our findings suggested that ER might effectively ameliorate the progression of COPD via JAK3/STAT3/NF-κB pathway in mice.


Ergosterol COPD JAK3/STAT3/NF-κB 



This work was supported by the National Twelve Five Major Drug Discovery Project (2011ZX09102-002-01). This research was supported by National Natural Science Foundation of China (No. 81274037).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Yang, G., Y. Wang, Y. Zeng, G.F. Gao, X. Liang, M. Zhou, et al. 2013. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. The Lancet 381: 1987–2015.CrossRefGoogle Scholar
  2. 2.
    Preobrazhenska, O., J.L. Wright, and A. Churg. 2012. Regional heterogeneity in murine lung fibroblasts from normal mice or mice exposed once to cigarette smoke. PLoS One 7: e39761.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Guo, T., and Y.Y. Li. 2012. Progresses on pharmacological and toxicological effects of Dengzhanxixin injection. Zhong Guo Zhong Yao Za Zhi 37(18): 2820–2823.Google Scholar
  4. 4.
    Wei, X., X.Q. Ye, Y.M. Xie, et al. 2011. Post-marketed re-evaluation of fleabane injection and Dengzhan Shengmai capsule study on treatment in patients with ischemic stroke. Zhong Guo Zhong Yao Za Zhi 36(20): 2789–2792.Google Scholar
  5. 5.
    Shen, W., L. Wang, R. Pi, Z. Li, and Rikang Wang. 2015. L-F001, a multifunctional ROCK inhibitor prevents paraquat-induced cell death through attenuating ER stress and mitochondrial dysfunction in PC12 cells. Biochemical and Biophysical Research Communications 464(3): 794–799.CrossRefPubMedGoogle Scholar
  6. 6.
    Chen, T., Y. Mou, J. Tan, L. Wei, Y. Qiao, T. Wei, P. Xiang, S. Peng, Y. Zhang, Z. Huang, and H. Ji. 2015. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. International Immunopharmacology 25: 55–64.CrossRefPubMedGoogle Scholar
  7. 7.
    Shilin, G., L. Weiran, X. Zhilin, W. Shumin, and Y. Tianhua. 2016. Alleviation effects of lycoperdon pedicellatum peck. on lipopolysaccharide-induced acute lung injury in mice. Evidence-based Complementary and Alternative Medicine 501: 1809715.Google Scholar
  8. 8.
    Shi, H.L., J.B. Liu, and A.P. Lu. 2016. Expression profiles of PI3K, NF-κB, and STAT1 in peripheral blood mononuclear cells in children with bronchial asthma. Zhongguo Dang Dai Er Ke Za Zhi 18(7): 614–617.PubMedGoogle Scholar
  9. 9.
    Gao, Y., L. Zhaoyu, F. Xiangming, L. Chunyi, P. Jiayu, S. Lu, C. Jitao, C. Liangcai, and L. Jifang. 2016. Abietic acid attenuates allergic airway inflammation in a mouse allergic asthma model. International Immunopharmacology 38: 261–266.CrossRefPubMedGoogle Scholar
  10. 10.
    Song, C., L. He, J. Zhang, H. Ma, X. Yuan, G. Hu, L. Tao, J. Zhang, and J. Meng. 2016. Fluorofenidone attenuates pulmonary inflammation and fibrosis via inhibiting the activation of NALP3 inflammasome and IL-1β/IL-1R1/MyD88/NF-κB pathway. Journal of Cellular and Molecular Medicine 20(11): 2064–2077.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Tang, H., L. Gao, J. Mao, H. He, J. Liu, X. Cai, H. Lin, and T. Wu. 2016. Salidroside protects against bleomycin-induced pulmonary fibrosis: activation of Nrf2-antioxidant signaling, and inhibition of NF-κB and TGF-β1/Smad-2/-3 pathways. Cell Stress & Chaperones 21(2): 239–249.CrossRefGoogle Scholar
  12. 12.
    Zhang, C., S. Qin, L. Qin, L. Liu, W. Sun, X. Li, N. Li, R. Wu, and X. Wang. 2016. Cigarette smoke extract-induced p120-mediated NF-κB activation in human epithelial cells is dependent on the RhoA/ROCK pathway. Science Reports 6: 23131.CrossRefGoogle Scholar
  13. 13.
    Yang, M., Y. Wang, Y. Zhang, F. Zhang, Z. Zhao, S. Li, J. Zhang, X. Cao, and D. Zhang. 2016. S-allylmercapto-l-cysteine modulates MUC5AC and AQP5 secretions in a COPD model via NF-кB signaling pathway. International Immunopharmacology 39: 307–313.CrossRefPubMedGoogle Scholar
  14. 14.
    Zhang, S.Y., L.T. Xu, A.X. Li, and S.M. Wang. 2015. Effects of ergosterol, isolated from scleroderma polyrhizum pers., on lipopolysaccharide-induced inflammatory responses in acute lung injury. Inflammation 38(5): 1979–1985.CrossRefPubMedGoogle Scholar
  15. 15.
    Nallathamby, N., L. Guan-Serm, S. Vidyadaran, S.N. Abd Malek, J. Raman, and V. Sabaratnam. 2015. Ergosterol of Cordyceps militaris attenuates LPS induced inflammation in BV2 microglia cells. Natural Product Communications 10(6): 885–886.PubMedGoogle Scholar
  16. 16.
    Sevenoaks, M.J., and R.A. Stockley. 2006. Chronic obstructive pulmonary disease, inflammation and co-morbidity—a common inflammatory phenotype? Respiratory Research 7: 1.CrossRefGoogle Scholar
  17. 17.
    J. P. Hanrahan, C. B. Sherman, E. A. Bresnitz, K. M. Emmons, D. M. Mannino. 1996. Cigarette smoking and health. American Thoracic Society, American Journal of Respiratory and Critical Care Medicine 153.Google Scholar
  18. 18.
    Tuder, R.M., and J.H. Yun. 2008. It takes two to tango: cigarette smoke partners with viruses to promote emphysema. The Journal of Clinical Investigation 118: 2689–2693.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Yoshida, T., I. Mett, A.K. Bhunia, J. Bowman, M. Perez, L. Zhang, et al. 2010. Rtp801, a suppressor of mTOR signaling, is an essential mediator of cigarette smoke-induced pulmonary injury and emphysema. Nature Medicine 16: 767–773.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fischer, B.M., E. Pavlisko, and J.A. Voynow. 2011. Pathogenic triad in COPD: oxidative stress, protease-antiprotease imbalance, and inflammation. International Journal of Chronic Obstructive Pulmonary Disease 6: 413.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jiang, W., F. Luo, Q. Lu, J. Liu, P. Li, X. Wang, et al. 2016. The protective effect of Trillin LPS-induced acute lung injury by the regulations of inflammation and oxidative state. Chemico-Biological Interactions 243: 127–134.CrossRefPubMedGoogle Scholar
  22. 22.
    Chen, T., W. Jiang, H. Zhang, X. You, M. Liu, L. Wang, et al. 2016. Protective effect of trillin against ethanol-induced acute gastric lesions in an animal model. RSC Advances 6: 20081–20088.CrossRefGoogle Scholar
  23. 23.
    Chen, T., R. Wang, W. Jiang, H. Wang, A. Xu, G. Lu, et al. 2016. Protective effect of astragaloside IV against paraquat-induced lung injury in mice by suppressing rho signaling. Inflammation 39: 483–492.CrossRefPubMedGoogle Scholar
  24. 24.
    Zhu, L., T. Wei, X. Chang, H. He, J. Gao, Z. Wen, et al. 2015. Effects of salidroside on myocardial injury in vivo in vitro via regulation of Nox/NF-kappaB/AP1 pathway. Inflammation 38: 1589–1598.CrossRefPubMedGoogle Scholar
  25. 25.
    Chen, T., L. Xiao, L. Zhu, S. Ma, T. Yan, and H. Ji. 2015. Anti-asthmatic effects of ginsenoside Rb1 in a mouse model of allergic asthma through relegating Th1/Th2. Inflammation 38: 1814–1822.CrossRefPubMedGoogle Scholar
  26. 26.
    Jiang, W., R. Zhou, P. Li, Y. Sun, Q. Lu, Y. Qiu, et al. 2016. Protective effect of chrysophanol on LPS/d-GalN-induced hepatic injury through the RIP140/NF-κB pathway. RSC Advances 6: 38192–38200.CrossRefGoogle Scholar
  27. 27.
    Jing, W., M. Chunhua, and W. Shumin. 2015. Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-kappaB pathway in vivo and in vitro. Toxicology and Applied Pharmacology 285: 128–135.CrossRefPubMedGoogle Scholar
  28. 28.
    Ma, C., L. Zhu, J. Wang, H. He, X. Chang, J. Gao, et al. 2015. Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3K/Akt/mTOR signaling pathway. Journal of Ethnopharmacology 168: 349–355.CrossRefPubMedGoogle Scholar
  29. 29.
    Chen, T., J. Gao, P. Xiang, Y. Chen, J. Ji, P. Xie, et al. 2015. Protective effect of platycodin D on liver injury in alloxan-induced diabetic mice via regulation of Treg/Th17 balance. International Immunopharmacology 26: 338–348.CrossRefPubMedGoogle Scholar
  30. 30.
    Brusselle, G., K. Bracke, T. Maes, A. D’hulst, K. Moerloose, G. Joos, et al. 2006. Murine models of COPD. Pulmonary Pharmacology & Therapeutics 19: 155–165.CrossRefGoogle Scholar
  31. 31.
    Pauwels, R.A., and K.F. Rabe. 2004. Burden and clinical features of chronic obstructive pulmonary disease (COPD). The Lancet 364: 613–620.CrossRefGoogle Scholar
  32. 32.
    Krommidas, G., K. Kostikas, G. Papatheodorou, A. Koutsokera, K.I. Gourgoulianis, C. Roussos, et al. 2010. Plasma leptin and adiponectin in COPD exacerbations: associations with inflammatory biomarkers. Respiratory Medicine 104: 40–46.CrossRefPubMedGoogle Scholar
  33. 33.
    Jiang, Q., M. Yi, Q. Guo, C. Wang, H. Wang, S. Meng, et al. 2015. Protective effects of polydatin on lipopolysaccharide-induced acute lung injury through TLR4-MyD88-NF-kappaB pathway. International Immunopharmacology 29: 370–376.CrossRefPubMedGoogle Scholar
  34. 34.
    Profita, M., G. Chiappara, F. Mirabella, R. Di Giorgi, L. Chimenti, G. Costanzo, et al. 2003. Effect of cilomilast (Ariflo) on TNF-α, IL-8, and GM-CSF release by airway cells of patients with COPD. Thorax 58: 573–579.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Chen, T., Q. Guo, H. Wang, H. Zhang, C. Wang, P. Zhang, et al. 2015. Effects of esculetin on lipopolysaccharide (LPS)-induced acute lung injury via regulation of RhoA/Rho Kinase/NF-kB pathways in vivo and in vitro. Free Radical Research 49: 1459–1468.CrossRefPubMedGoogle Scholar
  36. 36.
    Zhang, K., J. Liu, X. You, P. Kong, Y. Song, L. Cao, et al. 2016. P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice. Neuroscience Letters 613: 60–65.CrossRefPubMedGoogle Scholar
  37. 37.
    Wiesner, C., G. Winsauer, U. Resch, M. Hoeth, J. Schmid, J. van Hengel, et al. 2008. α-Catulin, a Rho signalling component, can regulate NF-κB through binding to IKK-β, and confers resistance to apoptosis. Oncogene 27: 2159–2169.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal FungiJilin Agricultural University JilinChangchunChina
  2. 2.Changchun University of Chinese MedicineChangchunChina

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